Sarah Bening (COLLINS LAB)

Sensitizing Tolerant Bacteria to Beta-lactam Antibiotics

Bacterial tolerance to antibiotic killing can lead to chronic, costly infections, from which resistance may emerge. Here we show that metabolic stimulation sensitizes tolerant bacteria to beta-lactam antibiotics, one of our oldest and most widely used classes of antimicrobials. We demonstrate that supplementation with D-amino acids further potentiates beta-lactam lethality, and that this combination approach can be coupled with beta-lactamase inhibitors to sensitize and treat tolerant cultures of resistant pathogens.

Noor Momin (WITTRUP LAB)

Collagen Anchoring of Intratumorally Administered Cytokines Safely Potentiates Cancer Immunotherapy

The clinical application of cytokine therapies for cancer treatment remains limited due to adverse reactions and insufficient therapeutic effects. Improving the therapeutic index of cytokines can be achieved by better localizing their effects to the tumor. We find that intratumoral administration of a cytokine fused to a collagen-binding protein prolongs local retention and dramatically reduces systemic exposure. Cytokine collagen-anchoring is a facile, tumor-agnostic strategy to safely potentiate otherwise marginally effective immunotherapies.